Impact of socioeconomic status on survival after CD19 CART therapy.
Authors: Haley Newman, Yimei Li, Hongyan Liu, Vicky Tam, Regina M Myers, Amanda M DiNofia, Colleen Callahan, Claire M White, Diane Baniewicz, Stephan Kadauke, Caroline Diorio, David T. Teachey, Susan R. Rheingold, Kelly D. Getz, Carl H. June, Richard Aplenc, Shannon L. Maude, Stephan A. Grupp, Kira Bona, Allison Emily Barz Leahy
Journal: Journal of Clinical Oncology (2022)

7013 Background: CD19-directed chimeric antigen receptor T cell (CART) therapy has dramatically improved survival for children with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). While significant socioeconomic (SES) outcome disparities exist for children with newly diagnosed B-ALL, the impact of SES on CART access and outcomes is poorly described. Using the largest single-center pediatric CART experience, we investigated the hypothesis that poverty-exposed children would have inferior survival outcomes compared to unexposed children. Methods: Retrospective cohort study of US pediatric patients treated on CD19 CART clinical trials or with commercial tisagenlecleucel at Children's Hospital of Philadelphia from 2012-2020. Poverty was the primary exposure, defined at the household-level by insurance status (public vs private). Neighborhood opportunity was defined by census-derived Childhood Opportunity Index (COI) (low [q1-2] vs high [q3-4]). Overall survival (OS) and relapse-free survival (RFS) were evaluated by Kaplan Meier methods, and association with exposures by Cox regression models. Results: Among 206 patients, 36% were household poverty exposed, 24.9% low COI, 21.4% identified as Hispanic, 7.3% non-Hispanic Black, 63.6% non-Hispanic White, and 7.7% non-Hispanic Other. Household-poverty exposure was similar between local and referred patients (32.4% vs 36.7%). Patients unexposed to poverty at the household level or with high COI presented to CART with high disease burden (37.1% vs 26%, p = 0.049, 37.9% vs. 29.7%, p = 0.002). In multivariate analysis adjusting for age, race/ethnicity, disease burden, relapse status, and inotuzumab exposure, there were no significant differences in OS by householdverty (HR 0.86, 95%CI 0.50-1.48, p = 0.575) or low COI (HR 1.03, 95%CI 0.53-1.99, p = 0.932). Low COI was associated with inferior RFS (HR 2.26, 95%CI 1.34-8.80, p = 0.002). There was no significant difference in RFS by household-poverty (HR 0.84, 95%CI 0.48-1.44, p = 0.520). Conclusions: Household poverty was not associated with inferior survival outcomes in pediatric patients who received CART for r/r B-ALL. Patients with low neighborhood opportunity had increased hazard of relapse, a finding that requires investigation of the COI components underlying this association. Patients of higher proxied SES were more likely to have high disease burden, an access inequity potentially reflecting referral pattern bias or greater ability of advantaged families to advocate for CART. Future institutional and multi-center studies should utilize patient-reported social determinants of health to investigate mechanisms driving these disparities and guide care delivery interventions to improve equity in access and outcomes. Clinical trials: NCT01626495, NCT02435849, NCT02374333, NCT02228096, NCT02906371